Biomedical subjects

T F Fok

Publications and source records attributed to T F Fok.

At least 91 records · Page 5Linked to original sources

PubMed2001

Platelet-derived growth factor enhances granulopoiesis via bone marrow stromal cells.

Platelet-derived growth factor (PDGF), a growth factor for connective tissue cells, stimulates erythropoiesis and megakaryocytopoiesis in vitro but the effect of PDGF on granulocyte proliferation remains unknown. The effect of the recombinant human PDGF-BB isoform on granulopoiesis was investigated in this study. The results show that PDGF significantly stimulated murine colony-forming unit-granulocyte-monocyte (CFU-GM) proliferation in a dose-dependent manner (1 to 100 ng/mL) using murine bone marrow cells (n = 4). Maximum stimulation was obtained with 50 ng/mL of PDGF (P < .01). The effect of PDGF on murine CFU-GM proliferation was compared with that of interleukin (IL)-3, IL-6, granulocyte-monocyte colony-stimulating factor (GM-CSF), and acidic fibroblast growth factor (aFGF) at their optimal doses. The stimulating activity of PDGF was higher than that of aFGF but lower than that of IL-3, IL-6, or GM-CSF. There is no synergistic effect between PDGF and IL-3 or IL-6, but a significant enhancing effect was observed in IL-3 plus IL-6. PDGF also stimulated the growth of CFU-GM with CFU-megakaryocyte in the presence of bone marrow stromal cells. We also found that PDGF had similar a effect on human CFU-GM proliferation using bone marrow mononuclear cells (MNC). However, the increase in PDGF-stimulated CFU-GM proliferation was inhibited by anti-GM-CSF, anti-IL-3, and anti-IL-6 antibodies (n = 4), suggesting that endogenously produced GM-CSF, IL-3, and IL-6 may play a role in the PDGF-induced CFU-GM proliferation. Furthermore, PDGF (1 to 100 ng/mL) did not show any effect on CFU-GM proliferation when replacing bone marrow MNC with immunomagnetic selection-enriched CD34+ cells from human cord blood (n = 5; purity, 91% +/- 6.5%). This study indicates that PDGF may indirectly enhance CFU-GM proliferation by inducing the bone marrow stromal cells to produce GM-CSF, IL-3, or IL-6.

Adult↗

PubMed2001

Oxygen consumption by lungs with acute and chronic injury in a rabbit model.

OBJECTIVE: To study the oxygen consumption by lungs with acquired acute and chronic injury in a rabbit model. DESIGN: A non-randomized controlled animal study. SUBJECTS AND METHOD: Three groups of White New Zealand rabbits were studied to determine the oxygen consumption of the lungs. Group 1 (n=21, controls) consisted of healthy rabbits with normal lungs. The rabbits in group 2 (n=14) had sustained acute lung damage induced by subcutaneous N-nitroso-N-methylurethane and those in group 3 (n=9) had sustained chronic lung damage inflicted by a single dose of intra-tracheal bleomycin. Pulmonary oxygen consumption was estimated from the difference between the whole body oxygen consumption, measured by indirect calorimetry, and systemic oxygen consumption estimated by the Fick method. MEASUREMENTS AND RESULTS: Both acute and chronic lung-damaged groups had significantly greater pulmonary oxygen consumption than the control group, both as absolute values [control vs acute vs chronic: 0.25 (0.04) vs 0.76 (0.10) vs 1.77 (0.21) ml/kg per min, p<0.001], and as a percentage of total body oxygen consumption [2.98 (0.47) vs 9.34 (1.39) vs 20.20 (2.11)%, p<0.0001]. Histological evaluation of the severity of lung damage using a lung-injury score revealed significantly higher scores in both lung-injury groups than in the controls. CONCLUSIONS: These findings suggest that the lung is an important site of energy loss in subjects with acute and chronic lung injury.

Acute Disease↗

PubMed2001

Overview of common inherited metabolic diseases in a Southern Chinese population of Hong Kong.

BACKGROUND: The Joint metabolic clinic at the Prince of Wales Hospital was established in January 1997 to provide a comprehensive multi-disciplinary care to patients with inherited metabolic diseases (IMDs). Patients are referred from both within and outside our hospital. Until July, 2000, more than 40 patients and families with 20 different biochemical diagnoses attend the clinic for regular follow up. A pattern of more common IMDs among Hong Kong Chinese emerged from our case registry. In order to advance the understanding of Chinese metabolic diseases, we examined the molecular basis of those diseases with unique features in Chinese or were locally prevalent. Mutations were found in patients with primary carnitine deficiency, ornithine transcarbamylase deficiency, X-linked adrenoleukodystrophy, glutaric aciduria type I, and galactosemia. We also analyzed the mutations in multiple carboxylase deficiency and Niemann-pick type C on four families. CONCLUSIONS: Although IMDs are a significant cause of mortality and morbidity among pediatric patients, with a better understanding of the molecular genetics of these diseases, prenatal diagnosis of these common IMDs will be facilitated, which is currently the most effective way of controlling IMDs.

Fatty Acids↗

PubMed2001

Platelet-derived growth factor enhances ex vivo expansion of megakaryocytic progenitors from human cord blood.

Infusion of ex vivo expanded megakaryocytic (MK) progenitor cells is a strategy for shortening the duration of thrombocytopenia after haematopoietic stem cell transplantation. The cell dose after expansion has emerged as a critical factor for achieving the desired clinical outcomes. This study aimed to establish efficient conditions for the expansion of the MK lineage from enriched CD34(+) cells of umbilical cord blood and to investigate the effect of platelet-derived growth factor (PDGF) in this system. Our results demonstrated that thrombopoietin (TPO) alone produced a high proportion of CD61(+)CD41(+) cells but a low total cell count and high cell death, resulting in an inferior expansion. The addition of interleukin-1 beta (IL-1 beta), Flt-3 ligand (Flt-3L) and to a lesser extent IL-3 improved the expansion outcome. The treatment groups with three to five cytokines produced efficient expansions of CFU-MK up to 400-fold with the highest yield observed in the presence of TPO, IL-1 beta, IL-3, IL-6 and Flt-3L. CD34(+) cells were expanded by five to 22-fold. PDGF improved the expansion of all cell types with CD61(+)CD41(+) cells, CFU-MK and CD34(+) cells increased by 101%, 134% and 70%, respectively. On day 14, the CD61(+) population consisted of diploid (86.5%), tetraploid (11.8%) and polyploid (8N--32N; 1.69%) cells. Their levels were not affected by PDGF. TPO, IL-1 beta, IL-3, IL-6, Flt-3L and PDGF represented an effective cytokine combination for expanding MK progenitors while maintaining a moderate increase of CD34(+) cells. This study showed, for the first time, that PDGF enhanced the ex vivo expansion of the MK lineage, without promoting their in vitro maturation. PDGF might be a suitable growth factor to improve the ex vivo expansion of MK progenitors for clinical applications.

Antigens, CD↗

PubMed2001

Neonatal jaundice--traditional Chinese medicine approach.

Herbal treatment of neonatal jaundice (NNJ) has been practiced in China for a long time. Even to-date, a variety of herbal items, including "Yin-chin" (Artemisia), "Huang-qin" (Scutellaria), "Da-huang" (Rheum officinale), "Gan-cao" (Glycyrrhiza), and "Huang-lin" (Coptis chinesis), are still being prescribed to jaundiced infants, often in combination with modern treatment such as phototherapy and exchange transfusion. Their efficacy has, however, not been tested by properly conducted randomised controlled trial. On the other hand, exposure to herbs either before or after birth has been suspected to be a cause of hemolysis and jaundice in the newborns. It is also widely believed in the Chinese community that a number of herbal items are hemolytic agents in infants deficient in the enzyme glucose-6-phosphate dehydrogenase (G6PD). The belief is so deep rooted that each infant detected to have G6PD deficiency by neonatal cord blood screening is given a G6PD deficiency alert card, which states that the child must avoid these herb items for life. In a cohort of 1008 mother-infant pairs, however, we have previously shown that there was no association between maternal herb consumption during pregnancy and the incidence or severity of neonatal hyperbilirubinemia in their offsprings, including those who were deficient in G6PD. A thorough search of medical literature also fails to detect any evidence that any of the herbs stated in the G6PD deficiency alert card causes hemolysis in G6PD-deficient subjects. Thus, there are many misunderstandings and unsubstantiated beliefs about the relationship between herbal medicine and NNJ. Given the potential usefulness of Chinese traditional medicine, which has been practiced for almost 3000 years and is still gaining momentum in the modern days, extensive scientific studies to determine the therapeutic efficacy and potential harmful effects of the various herbal items are warranted.

Drugs, Chinese Herbal↗

PubMed2001

Temporal relationship between air pollution and hospital admissions for asthmatic children in Hong Kong.

BACKGROUND: Many epidemiological studies have shown positive association between respiratory health and current levels of outdoor air pollution in Europe and America. OBJECTIVE: The aim of this study was to investigate the association between air pollution and the number of childhood admissions for asthma in Hong Kong. METHODS: Daily counts of childhood admission for asthma to a large teaching Hospital were obtained from the computerized database for the period 1993-1994. A Poisson regression allowing for seasonal patterns and meteorological conditions was used to assess the associations between the number of Hospital admissions and the three pollutants: nitrogen dioxide, sulphur dioxide and inhalable particles (measured as PM10, particles < 10 microm in aerodynamic diameter). RESULTS: A total of 1217 children under 15 years of age were admitted for asthma during the study period. The calculated annual hospitalization rates were 283 and 178 per 100 000 for boys and girls, respectively. The mean PM10, NO2 and SO2 levels were 44.1 microg/m3, 43.3 microg/m3, and 12.2 microg/m3, respectively. Daily admission for asthma increased significantly with increasing ambient level of nitrogen dioxide (relative risk (RR) = 1.08 per 10 microg/m3 increase), sulphur dioxide (RR = 1.06) and inhalable particles (RR = 1.03). No association was found between hospital admission and humidity, temperature or atmospheric pressure. CONCLUSION: This is the first daily time series study of childhood admissions for asthma and air pollution in Hong Kong. The results support that current levels of air pollution contribute to the respiratory morbidity in asthmatic children in Hong Kong.

Adolescent↗

PubMed2001

Prevalence of respiratory and atopic disorders in Chinese schoolchildren.

BACKGROUND: Epidemiological surveys have shown that the prevalence of asthma in the Asian population is relatively low. Within the Chinese population, schoolchildren from Hong Kong were found to have the highest rate of asthma. OBJECTIVE: To compare the prevalence of respiratory and atopic disorders, and to assess the role of atopy in the development of asthma, in Chinese schoolchildren from Hong Kong, Beijing and Guangzhou. METHODS: Community-based random samples of schoolchildren aged 9-11 years from three Chinese cities (Hong Kong, Beijing and Guangzhou) were recruited for study using the International Study of Asthma and Allergies in Childhood (ISAAC) Phase II protocol. Subjects were studied by parental questionnaires (n = 10902), skin-prick tests (n = 3479) and skin examination (n = 3479). RESULTS: The prevalence rates of current wheeze, speech limiting wheeze, rhinoconjunctivitis and flexural dermatitis were significantly more common in Hong Kong than in Beijing or Guangzhou. The atopy rate was also higher in Hong Kong (41.2%) than in Beijing (23.9%) or Guangzhou (30.8%). Atopy was strongly correlated with current wheeze (OR 7.74; 95% CI = 5.70-10.51). Subgroup analyses of children from Hong Kong revealed that children born in mainland China who had subsequently migrated to Hong Kong had a significantly lower rate of allergic symptoms and atopy than those children born in Hong Kong. CONCLUSION: Using a standardized written questionnaire along with a skin prick test and skin examination, we confirmed that the prevalence of asthma, allergic diseases and atopy was highest in schoolchildren from Hong Kong. Atopic sensitization is an important factor associated with asthma in Chinese children.

Asian People↗

PubMed2001

Changes of leptin and metabolic hormones in preterm infants: a longitudinal study in early postnatal life.

OBJECTIVES: Very little is known concerning the physiological role of leptin and growth in the early postnatal period and the association of leptin with other metabolic hormones in preterm infants. This study aims to investigate these relationships, and to explore the longitudinal and dynamic profile of leptin and metabolic hormones including insulin, ACTH, cortisol and FT4 in this category of patient. We also postulate that a rapid increase in body weight and body mass index in the first few weeks of life may be associated with a corresponding increase in serum leptin if the 'adipoinsular axis' is active at this stage. DESIGN: A longitudinal study in a cohort of preterm infants < 34 weeks gestation for the first five weeks of postnatal life. PATIENTS AND METHODS: Sixty-one preterm newborns < 34 weeks gestation were prospectively enrolled. Blood samples were collected in the morning when the newborns were 24 h of age (day 1), and on days 5, 14 and 35 of life. Serum leptin, insulin, cortisol, FT4, glucose and plasma ACTH concentrations were analysed using standard biochemical methods. Spearman's correlation coefficient was used to assess the inter-relationship of different metabolic hormones on the first day of life, and the relationship between metabolic hormones on day 1 and anthropometric or clinical parameters. The mixed-effects models were further used for analysing the multiple longitudinal measurements, and also for comparing the hormone concentrations between day 1 (baseline) and their corresponding levels on days 5, 14 and 35. RESULTS: Serum leptin on day 1 (baseline) was significantly associated with serum insulin (r = 0.30, P < 0.05) and insulin:glucose ratio (r = 0.29, P < 0.05) in infants < 34 weeks gestation. Female preterm infants had significantly higher serum leptin (P < 0.05) and insulin (P < 0.05) levels than male infants. In addition, the duration between the last dose of antenatal dexamethasone and delivery significantly influenced the serum concentrations of leptin (r = - 0.27, P < 0.05), cortisol (r = 0.52, P < 0.001), plasma ACTH (r = 0.28, P < 0.05) and insulin:glucose ratio (r = - 0.27, P < 0.05) on the first day of life. Despite significant increase in body weight (P < 0.00001) and body mass index (P < 0.00001) by day 35 when compared to birth weight, no corresponding significant changes were observed for serum leptin, insulin and FT4. However, there was an increasing though statistically nonsignificant trend in serum leptin after day 14 of life. CONCLUSION: This study characterized the longitudinal profile of leptin and metabolic hormones in preterm infants < 34 weeks gestation in the first 5 weeks of life. Serum leptin was significantly associated with serum insulin and insulin:glucose ratio supporting the hypothesis that an 'adipoinsular axis' exists and is likely to be functional before 34 weeks of gestation. Although a significant increase in body weight was demonstrated by day 35, no significant corresponding changes occurred with regard to serum leptin. We postulate that the limited quantity of adipose tissue at this stage of development might have contributed to this observation. Moreover, our results also showed that the duration between the last dose of antenatal corticosteroid and delivery could influence the postnatal concentrations of adipoinsular and pituitary-adrenal hormones. Thus, it is possible that antenatal dexamethasone might affect fetal growth and development via these neuroendocrine pathways in early intrauterine life.

Adrenocorticotropic Hormone↗

PubMed2001

Haematopoietic stem and progenitor cells in human term and preterm neonatal blood.

BACKGROUND AND OBJECTIVES: Whilst cord blood (CB) contains a significant number of haematopoietic stem and progenitor cells suitable for bone marrow transplantation, levels of these cells are very low in the adult circulation. In previous studies, we demonstrated that stem and progenitor cells are present in neonatal blood (NB) and reported the first sibling transplant using a combination of CB and NB for a patient with beta-thalassaemia major. However, our preliminary data showed that the number of CD34+ cells decreased rapidly in the peripheral blood of neonates soon after birth. To further investigate the mechanism of the change of stem and progenitor cells in NB, we measured the steady-state levels of CD34+ cells, early progenitor subsets and the expression of adhesion molecules, in term and preterm neonates. MATERIALS AND METHODS: NB was collected serially from infants at 2, 4, 6, 8, 24 and 48 h after birth and was analysed by three-colour flow cytometry. RESULTS: Our results demonstrated that the number of CD34+ cells rapidly decreased in term NB, particularly during the first 2-6 h of life, by 29.2 +/- 5.55% (P = 0.0003) in absolute counts/ml. A decrease was observed in all subsets of CD34+ cells studied, including the CD33+, CD71+, CD62L+ and CD49d+ populations. In contrast, the CD34+ cell number increased in preterm infants in the first 8 h of life, before starting to decrease. Significant inverse correlations were observed between gestational age and levels of CD34+ cells (P = 0.0065, 4-h collection time-point). CONCLUSION: Our study suggests that changes in the levels of CD34+ stem and progenitor cells in NB might be triggered by parturition and affected by the gestational age. Our findings confirmed that if targeted as a supplementary source of stem and progenitor cells to CB for transplantation, NB should be collected as soon as possible after birth.

Antigens, CD34↗

PubMed2001

Normal pulse oximeter reading in a cyanotic infant.

A newborn infant who presented with central cyanosis was found to have hereditary methaemoglobinaemia. The pulse oximeter readings and physical findings were incompatible. Clinical assessment remains an important part in the management of such cases.

Cyanosis↗

PubMed2001

Deceptive hyperbilirubinaemia in a newborn with familial lipoprotein lipase deficiency.

A rare case of familial lipoprotein lipase (LPL) deficiency in a Chinese newborn who presented with severe hyperbilirubinaemia is described. The falsely high serum bilirubin concentration was subsequently found to be a laboratory analytical error caused by interference of optical measurement of the lipaemic serum. Hypertriglyceridaemia and chylomicronaemia could be safely and effectively controlled by a fat-restricted diet using either modified elementary milk formula fortified with protein, calories and minerals, or the commercially available special milk formula such as Monogen or Portagen. DNA sequence analysis of the patient showed a Leu252Arg mutation in exon 6 of both alleles of the LPL gene. Although the parents were unrelated, both were heterozygous carriers of the same genetic defect. Codon 252 in exon 6 appears to be a common and critical site of mutation in the LPL gene of Chinese, but this important association has not been recognized previously.

Antigens, Differentiation↗

PubMed2001

Rhabdomyolysis following status asthmaticus.

A 15-year-old Chinese boy developed rhabdomyolysis with myoglobinuria and marked elevation of serum creatine phosphokinase following a prolonged and severe attack of asthma. He recovered after vigorous hydration and supportive treatment. Clinicians should be aware of this potentially fatal, albeit rare, complication of status asthmaticus.

Adolescent↗

PubMed2001

Dextran sedimentation in a semi-closed system for the clinical banking of umbilical cord blood.

BACKGROUND: The results of current processing procedures for reducing volume and recovering HPCs from umbilical cord blood (UCB) before cryopreservation vary. STUDY DESIGN AND METHODS: Dextran was added to bags containing UCB, followed by sedimentation for 30 minutes. The processed UCB was then frozen. RBCs, nucleated cells, MNCs, CD34+ cells, CFUs and long-term culture-initiating cells (LTC-ICs), viability, and sterility were evaluated. Fractionations in ficoll-hypaque and hydroxyethyl starch (HES) were also run in parallel for comparison. RESULTS: The nucleated cell (NC) recovery and RBC depletion were 86.1 percent and 94.3 percent, respectively (n = 50). Sedimentation with dextran also enabled the recovery of 80.7 percent MNCs and 82.6 percent CD34+ cells (n = 30). Postsedimentation samples displayed no impairment of CFU growth (n = 42, 108.7% CFU-C, 104.6% CFU-GEMM, 107% CFU-GM, and 95.7% BFU-E). Long-term cultures on five paired samples before and after sedimentation generated similar numbers of CFU-C each week (p = 0.88). Limiting dilution analysis of 12 paired pre/postsedimentation samples showed comparable median proportions of LTC-ICs (1/6494 vs. 1/5236; p = 0.18). The cell viability of 24 samples of thawed UCB after sedimentation was 90.3 percent (77.5-96%) and the recovery of CFU-C, CFU-GEMM, CFU-GM, and BFU-E of 11 postsedimentation samples was 93.4 percent, 84.9 percent, 92.3 percent, and 83.4 percent, respectively. NC recovery was significantly higher after treatment with dextran than with ficoll-hypaque (n = 30; 88.5% vs. 29.1%; p<0.005) and HES treatment (n = 21; 88.5% vs. 76.4%; p = 0.004). However, MNCs, CD34+ cells, CFUs, LTC-ICs, and RBCs were comparable. Two cycles of dextran sedimentation recovered 93.9 percent of NCs with cell viability of 98.6 percent (96.5-100%), whereas 11.7 percent of RBCs were retained (n = 20). The final yield volume was 33.5 (28-41) mL. CONCLUSION: In a semi-closed system, dextran sedimentation enabled volume reduction of UCB without significant quantitative and qualitative losses of HPCs.

Blood Banks↗

PubMed2001

Preclinical ex vivo expansion of cord blood hematopoietic stem and progenitor cells: duration of culture; the media, serum supplements, and growth factors used; and engraftment in NOD/SCID mice.

BACKGROUND: Ex vivo expansion of cord blood (CB) hematopoietic stem and progenitor cells increases cell dose and may reduce the severity and duration of neutropenia and thrombocytopenia after transplantation. This study's purpose was to establish a clinically applicable culture system by investigating the use of cytokines, serum-free media, and autologous plasma for the expansion of CB cells and the engraftment of expanded product in nonobese diabetic/severe combined immunodeficient (NOD/SCID) mice. STUDY DESIGN AND METHODS: Enriched CB CD34+ cells were cultured in four media (Iscove's modified Dulbecco's medium with FCS, Gibco; X-Vivo-10, BioWhittaker; QBSF-60, Quality Biological; and StemSpan SFEM, Stem Cell Technologies) with four cytokine combinations (thrombopoietin [TPO], SCF, Flt-3 ligand [FL] with and without G-CSF, and/or IL-6). The effect of autologous CB plasma was also investigated. The read-out measures were evaluated on Days 8 and 12. After expansion at the optimized condition, cultured cells were transplanted into sublethally irradiated NOD/SCID mice. The engraftment of human CD45+ cells and subsets in the bone marrow, spleen, and peripheral blood was determined. RESULTS: QBSF-60 or StemSpan SFEM supported high yields of early progenitors (CD34+ cells, <or= 64.8-fold; CD34+CD38- cells, 330-fold; CFU-granulocyte erythroid macrophage megakaryocyte [GEMM], 248-fold) and CFUs of the myeloid (CFU-GM, 407-fold) and erythroid (BFU/CFU-E, 144-fold) lineages. The expansion of the megakaryocytic lineage was consistently higher in X-Vivo-10 (CFU-megakaryocyte, 684-fold). Autologous plasma promoted colony formation but reduced CD34+ cells and CFU-GEMM. The addition of G-CSF or IL-6 improved cell yields; G-CSF was more effective for committed progenitors. Expansion products from cultures in QBSF-60 with the cytokines engrafted and differentiated into the myeloid and lymphoid lineages in NOD/SCID mice. CONCLUSION: The data supported the strategy of expansion. The optimized condition may be applicable to clinical expansion for the abrogation or reduction of posttransplant cytopenia.

Animals↗

PubMed2001

Manganese intake and cholestatic jaundice in neonates receiving parenteral nutrition: a randomized controlled study.

UNLABELLED: Infants requiring parenteral nutrition (n = 244) were randomized to receive either 1 (group 1, n = 121) or 0.0182 micromol/kg/d (group 2, n = 123) of manganese supplementation. The whole-blood manganese and serum direct bilirubin concentrations of the infants were monitored, as was the development of cholestasis (peak serum direct bilirubin concentration >50 micromol/L). Subgroup analysis was carried out on the data of 78 infants in group 1 and 82 in group 2 who had received manganese supplementation and more than three-quarters of their total daily fluid as parenteral nutrition for >14 d. Of all the infants randomized, the high manganese group (group 1) showed a trend towards developing higher peak whole-blood manganese concentration [group 1 versus group 2: median (interquartile range): 606.0 (421.0; 1005.0) vs 566.0 (336.0: 858.0); p=0.061] and higher peak serum direct bilirubin concentration [37.0 (10.5; 122.5) vs 19.0 (8.0; 112.5); p=0.153], but the differences between the 2 groups did not reach statistical significance. The 2 groups did not differ in terms of the occurrence of cholestasis during parenteral nutrition (63/121 vs 57/123; p=0.444). Subgroup analysis of infants who had received more than three-quarters of their total daily fluid as parenteral nutrition showed, however, that the high manganese group developed significantly higher whole-blood manganese concentration [743.5 (498.0; 1211.0) vs 587.0 (438.0; 982.0); p=0.037] and serum direct bilirubin concentration [84.0 (28.0; 170.0) vs 25.5 (9.0; 117.0): p < 0.001]. Although there was no significant difference in the occurrence of cholestasis (58/78 vs 49/82; p = 0.073), more infants in the high manganese group developed a more severe degree of direct hyperbilirubinaemia, with peak serum direct bilirubin >100 micromol/L (32/78 vs 20/82; p = 0.038). CONCLUSION: We conclude that the pathogenesis of parenteral nutrition-related cholestasis is probably multifactorial, and that high manganese intake is a significant contributory factor.

Cholestasis↗

PubMed2001

Hepatic iron storage in very low birthweight infants after multiple blood transfusions.

OBJECTIVE: To investigate the effect of multiple blood transfusions on hepatic iron storage in preterm, very low birthweight (VLBW) infants. METHODS: Seventeen VLBW infants who died within the first six months of life and underwent postmortem examination were studied. Serum ferritin, iron, and total iron binding capacity were measured within the week before the infants' death. Liver iron concentration was quantitatively determined by atomic absorption spectrophotometry and semiquantitatively assessed by histochemical liver iron grading. The clinical characteristics and the iron results were compared between infants receiving < 100 ml of blood (group A) and those receiving >/= 100 ml (group B). Spearman's correlation coefficient was used to evaluate the relation between the volume of blood transfused and serum/liver iron concentrations. Statistically significant variables associated with liver iron concentration were further subjected to multivariate stepwise regression analysis. RESULTS: Infants in group B had significantly higher serum iron (p < 0.01), serum ferritin (p < 0.01), and liver iron concentration (p < 0.01) than those in group A. The total and net volume of blood transfused were significantly associated with liver iron concentration (p < 0.001, r = 0.86; p < 0.001, r = 0.71 respectively), semiquantitative histochemical liver iron grading (p < 0.001, r = 0.80; p < 0.005, r = 0.71 respectively), and serum ferritin (p < 0.001, r = 0.84; p < 0.01, r = 0.69 respectively). In addition, both liver iron concentration and liver iron grading were found to be significantly associated with serum ferritin (p < 0.001, r = 0.76; p < 0.005, r = 0.68 respectively). Multivariate stepwise regression analysis indicated that the (log) liver iron concentration was significantly associated with the (log) volume of blood transfusion (p < 0.001; regression coefficient 0.39, SE 0.09), after adjustment for gestational age (R(2) = 0.84). CONCLUSIONS: This study showed a significant positive relation between the volume of blood transfused and the liver iron concentration in preterm VLBW infants. Although the transfusional blood volume correlated closely with the amount of iron deposited in hepatic tissues, clinical manifestations of iron overload were not observed. Carers should be aware of this potential harmful effect before prescribing blood or routine iron supplement to vulnerable preterm infants.

Blood Transfusion↗

PubMed2001

Refractory hypotension in preterm infants with adrenocortical insufficiency.

Five preterm, very low birthweight infants with severe hypotension and adrenocortical insufficiency are described. The profound hypotension was resistant to volume expansion and inotrope treatment, but responded promptly to corticosteroid treatment. A human corticotrophin releasing hormone (hCRH) test performed before corticosteroid treatment showed adequate pituitary response, and the endocrine dysfunction was identified at the adrenal level. Corticosteroid treatment should be considered and could be life saving in severely hypotensive preterm infants who do not respond to conventional treatment with volume expanders and inotropes.

Adrenal Insufficiency↗

PubMed2001

Randomised controlled study of oral erythromycin for treatment of gastrointestinal dysmotility in preterm infants.

AIM: To evaluate the effectiveness of oral erythromycin as a prokinetic agent for the treatment of moderately severe gastrointestinal dysmotility in preterm very low birthweight infants. METHODS: A prospective, double blind, randomised, placebo controlled study in a tertiary referral centre of a university teaching hospital was conducted on 56 preterm infants (< 1500 g) consecutively admitted to the neonatal unit. The infants were randomly allocated by minimisation to receive oral erythromycin (12.5 mg/kg, every six hours for 14 days) or an equivalent volume of placebo solution (normal saline) if they received less than half the total daily fluid intake or less than 75 ml/kg/day of milk feeds by the enteral route on day 14 of life. The times taken to establish half, three quarters, and full enteral feeding after the drug treatment were compared between the two groups. Potential adverse effects of oral erythromycin and complications associated with parenteral nutrition were assessed as secondary outcomes. RESULTS: Twenty seven and 29 infants received oral erythromycin and placebo solution respectively. The times taken to establish half, three quarters, and full enteral feeding after the drug treatment were significantly shorter in the group receiving oral erythromycin than in those receiving the placebo (p < 0.05, p < 0.05 and p < 0.0001 respectively). There was also a trend suggesting that more infants with prolonged feed intolerance developed cholestatic jaundice in the placebo than in the oral erythromycin group (10 v 5 infants). None of the infants receiving oral erythromycin developed cardiac dysrhythmia, pyloric stenosis, or septicaemia caused by multiresistant organisms. CONCLUSIONS: Oral erythromycin is effective in facilitating enteral feeding in preterm very low birthweight infants with moderately severe gastrointestinal dysmotility. Treated infants can achieve full enteral feeding 10 days earlier, and this may result in a substantial saving on hyperalimentation. However, until the safety of erythromycin has been confirmed in preterm infants, this treatment modality should remain experimental. Prophylactic or routine use of this medication for treatment of mild cases of gastrointestinal dysmotility is probably not warranted at this stage.

Double-Blind Method↗